Speaking during his weekly audience at Saint Peter's Square, the pope said: "May this pilgrimage be a happy occasion to reinforce understanding with our Orthodox brothers, by promoting more progress on the path toward fully uniting Christians."
The pontiff, who turns 81 on May 18, arrives in Athens on Friday and will then travel to Syria and Malta as part of his pilgrimage in the footsteps of the Apostle Paul.
"I also hope my visit to Syria, and in particular the Great Mosque of Damascus, will help reinforce inter-religious dialogue with followers of Islam by promoting an undertaking to work in favour of efficient and peaceful co-existence," the pope said.
The six-day tour, the 93rd since John Paul was elected in 1978, will begin under intense security in Greece, where there is widespread opposition to Catholics among the country's Christian Orthodox majority.
The pope will then travel on to predominantly Muslim Syria and then visit deeply Catholic Malta.
All three countries boast sites where the Apostle Paul, known as Saul of Tarsus before he converted to Christianity, carried out his missionary activity.